Wound infection is a serious issue because of multi-drug resistance bacteria, thus developing an advanced therapy is a needed demand. Photothermal therapy (PTT) is a novel noninvasive strategy that utilizes PTT agents to convert near-infrared (NIR) light energy into heat to kill living cells. In this work, we developed the PTT agent containing membrane to treat the wound infection for the first time. Palladium nanoparticles (PdNPs) were chosen as PTT agents owing to their high stability, good biocompatibility, excellent photothermal property, and simple-green preparation. Chitosan (CS) has been widely studied in tissue engineering due to its good properties such as biocompatible, biodegradable, antibacterial, and wound-healing abilities. However, the poor workability and high brittleness of CS limit the applications of CS in tissue engineering. Thus, we combined polyvinyl alcohol (PVA) and CS to have the membrane with high flexibility, wettability, highly porosity. The test on cells showed that the membrane has high biocompatibility. The combination of PdNPs loading CS/PVA membrane and laser irradiation killed most of the bacteria in vitro.

Background: Apolipoprotein A1 (APOA1) is a potential biomarker due its variable concentration in different types of cancers.

Objective: We for the first time evaluated the association between APOA1 -75 G/A, +83 C/T genotypes in tandem with APOA1 protein expression in urine samples to find out risk and potential relationship for differentially expressed urinary proteins and APOA1 genotypes.

Design: The study included 108 cases of bladder tumors and 150 healthy controls that were frequency matched to cases with respect to age, sex and smoking status. Genotyping was performed by PCR-RFLP and urinary expression of APOA1 protein was done by ELISA.

Results: Bladder tumor cases were significantly associated with APOA1-75 AA genotype (p<0.05) while as APOA1+83 CT heterozygotes showed association with cases (p<0.05). The overall distribution of different haplotypes showed a marked difference between cases and controls in GT when compared with wild type GC (p<0.03). Bladder tumor cases that carried variant genotype APOA1-75AA presented more (70.0%) with higher expression (≥20ng/ml) of APOA1 urinary protein and differed significantly against wild typeGG (p=0.03). Again, in low grade bladder tumors, urinary APOA1 protein significantly presented more (52.4% vs. 15.4% high grade) with higher expression (≥20ng) while high grade tumor cases (84.6% vs. 47.5% low grade) showed lower APOA1expression (<20ng/ml) (O.R= 6.08, p=0.002).

Conclusions: We found a strong association between APOA1-75G/A and risk for bladder tumor and its relation to urinary protein expression that substantiates its possible role as a marker for risk assessment of the disease and promising diagnostic marker for different grades of malignant bladder tumors

Key Words: Bladder cancer; APOA1; Genotype; Allele; Protein expression; Haplotype

In the process of searching for novel compounds with antipsychotic properties, structure-based virtual screening was conducted [1]. Among found dopamine D₂ receptor antagonists, the compound D2AAK3 with 115 nM affinity for D₂ receptor was identified. It also shows nanomolar or low micromolar affinity for D₁, D₃, 5-HT_1A, 5-HT_2A and 5-HT₇ receptors, what makes it a good candidate for a multi-target drug. Interactions of D2AAK3 with its molecular targets at the molecular level were studied in silico by performing homology modeling, molecular docking and molecular dynamics. The main contact of D2AAK3 with all studied receptors is the electrostatic interaction between the proton attached to the nitrogen atom of the ligand and the conserved Asp(3.32), what is typical for orthosteric binding mode in aminergic GPCRs. Behavioral studies [2] performed for D2AAK3 revealed that it decreases amphetamine-induced hyperactivity measured as spontaneous locomotor activity in mice, improves memory consolidation after acute treatment in passive avoidance test and exhibits anxiogenic activity 30 minutes after acute treatment in mice in elevated plus maze (this effect was reversed 60 minutes after administration of D2AAK3). Further optimization of reported compound, toward obtaining molecule with properties resembling atypical antipsychotics, will be conducted.

References:

1. Kaczor AA, Silva AG, Loza MI, Kolb P, Castro M, Poso A (2016) ChemMedChem 11:718-729.
2. Kaczor AA, Targowska-Duda KM, Budzyńska B, Biała G, Silva AG, Castro M (2016) Neurochemistry International 96:84-99.

20 million - this refers to the number of people who suffer from schizophrenia worldwide [1]. Hallucinations, distortions in thinking, abnormal motor behavior are the symptoms that impair the everyday life of people with schizophrenia and their families. Although numerous medications are available for this condition, many of them cause serious side effects, including agranulocytosis, sedation, or increased serum lipid concentration [2]. Extensive research has been carried out on dopamine D₂ receptors. Results of these studies suggest that there are links between the impaired dopaminergic neurotransmission and the presence of characteristic symptoms of the disease [3,4]. Thus providing this group of patients with potent dopamine D₂ receptor antagonists may benefit their treatment. Although multi-target ligands of aminergic G protein-coupled receptors (GPCRs) are most efficient as drugs for schizophrenia treatment, it should be emphasized that all marketed drugs against this disease are dopamine D₂ receptor antagonists or partial/biased agonists.

Computer-Aided Drug Design (CADD) techniques, in particular 3D-QSAR methods, are vital in developing novel ligands. Proper understanding of the structure-activity relationship can assist the design of novel drugs characterized by low toxicity and high efficacy [5]. The CoMFA method is a widely used 3D-QSAR approach that can be implemented to correlate the steric and the electrostatic properties of a series of molecules with their pharmacological activities.

Identification of a pharmacological gap in the treatment of schizophrenia became an incentive to thoughtfully examine the structure-activity relationship among a series of dopamine D₂ receptor antagonists. In our opinion, the constructed CoMFA model, characterized by good statistical parameters:(Q²=0.76, R²=0.92, F-value=338.9), will assist further drug design and enable to obtain ligands characterized by low toxicity and high bioactivity [6].

New sustainable ingredients with beneficial properties for health are a main goal for the food industry. In this regard, cocoa shell (CS) and coffee pulp (CP), by-products from the coffee and cocoa industry produced worldwide in large amounts, are suitable candidates. We previously stated these by-products are sources of phytochemicals and dietary fiber with potential hypolipidemic properties. This study aimed to assess the hypolipidemic properties of CS and CP after simulated gastrointestinal digestion. The capacities of the residual fraction of each digestion phase to bind bile salts and cholesterol and inhibit the lipase activity were measured to establish the in vitro hypolipidemic properties of both by-products. Furthermore, the digested fractions effect on lipid accumulation was evaluated in HepG2 cell line. From results, the CS showed higher ability to bind cholesterol (4-24%) and salts (2-3%) in gastric and colonic phases. Meanwhile, during gastrointestinal phase, CP showed a greater capacity to bind cholesterol (1-13%) and bile salts (2%). The capacity to inhibit lipase activity was more accentuated in the CS in gastrointestinal digestion (16%) and in CP during gastric digestion (11%). Likewise, the digested fractions of both by-products (100 µg/mL) significantly alleviated the accumulation of fat (17-20%) in the HepG2 cell model after the stimulation of cells with palmitic acid. This comparative approach suggests that both by-products exhibit similar hypolipidemic properties after in vitro digestion. This study promotes the revalorization of cocoa and coffee by-products as novel ingredients with potential beneficial properties to prevent chronic metabolic diseases due to their remarkable hypolipidemic properties.